Pathogenicity mechanisms at the mucosal interphase

In vitro translocation model simulates the intestinal epithelial barrier

In the healthy host, certain Candida species live as harmless commensals on mucosal surfaces like the oral, vaginal or intestinal mucosa. Under predisposing conditions, these Candida species growing on the oral or vaginal mucosa can cause tissue damage associated with induction of inflammation, immunopathology, and disease that significantly impacts quality of life.

When immune defense and microbiota are compromised in hospitalized patients or when the intestinal barrier is disturbed, fungal populations of the intestinal tract can invade the intestinal epithelial barrier and translocate into the bloodstream. From here, the fungus can infect virtually all organs and cause systemic fungal infection. Our aim is to elucidate which fungal and host factors mechanistically allow fungal adhesion to, invasion into, and damage of epithelial cells as well as translocation through intestinal barriers and invasion of host tissues.

To unravel host-pathogen interactions at the epithelial interface for C. albicans, but also C. glabrata and the newly emerged, multidrug-resistant species C. auris we are using in vitro infection models, genome-wide dual-species transcription profiling techniques, and fungal gene deletion strains.

Staff

Stefanie Allert
Lydia Kasper
Jakob Sprague

Publications

Arastehfar A, Boekhout T, Butler G, De Cesare GB, Dolk E, Gabaldón T, Hafez A, Hube B, Hagen F, Hovhannisyan H, Iracane E, Kostrzewa M, Lackner M, Lass-Flörl C, Llorens C, Mixão V, Munro C, Oliveira-Pacheco J, Pekmezovic M, Pérez-Hansen A, Sanchez AR, Sauer FM, Sparbier K, Stavrou AA, Vaneechoutte M, Vatanshenassan M (2019) Recent trends in molecular diagnostics of yeast infections: from PCR to NGS. FEMS Microbiol Rev 43(5), 517-547. (Review)
Bacher P, Hohnstein T, Beerbaum E, Röcker M, Blango MG, Kaufmann S, Röhmel J, Eschenhagen P, Grehn C, Seidel K, Rickerts V, Lozza L, Stervbo U, Nienen M, Babel N, Milleck J, Assenmacher M, Cornely OA, Ziegler M, Wisplinghoff H, Heine G, Worm M, Siegmund B, Maul J, Creutz P, Tabeling C, Ruwwe-Glösenkamp C, Sander LE, Knosalla C, Brunke S, Hube B, Kniemeyer O, Brakhage AA, Schwarz C, Scheffold A (2019) Human anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. Cell 176(6), 1340-1355.
Correia I, Prieto D, Román E, Wilson D, Hube B, Alonso-Monge R, Pla J (2019) Cooperative role of MAPK pathways in the interaction of Candida albicans with the host Epithelium. Microorganisms 8(1), 48.
Ho J, Yang X, Nikou SA, Kichik N, Donkin A, Ponde NO, Richardson JP, Gratacap RL, Archambault LS, Zwirner CP, Murciano C, Henley-Smith R, Thavaraj S, Tynan CJ, Gaffen SL, Hube B, Wheeler RT, Moyes DL, Naglik JR (2019) Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor. Nat Commun 10(1), 2297.
Ikonomova SP, Moghaddam-Taaheri P, Wang Y, Doolin MT, Stroka KM, Hube B, Karlsson AJ (2019) Effects of histatin 5 modifications on antifungal activity and kinetics of proteolysis. Protein Sci 29(2), 480-493.
Ishchuk OP, Ahmad KM, Koruza K, Bojanovič K, Sprenger M, Kasper L, Brunke S, Hube B, Säll T, Hellmark T, Gullstrand B, Brion C, Freel K, Schacherer J, Regenberg B, Knecht W, Piškur J (2019) RNAi as a tool to study virulence in the pathogenic yeast Candida glabrata. Front Microbiol 10, 1679.
Naglik JR, Gaffen SL, Hube B (2019) Candidalysin: Discovery and function in Candida albicans infections. Curr Opin Microbiol 52, 100-109. (Review)
Pekmezovic M, Mogavero S, Naglik JR, Hube B (2019) Host-pathogen interactions during female genital tract infections. Trends Microbiol 27(12), 982-996. (Review)
Swidergall M, Khalaji M, Solis N, Moyes D, Drummond R, Hube B, Lionakis M, Murdoch C, Filler S, Naglik J (2019) Candidalysin is required for neutrophil recruitment and virulence during systemic Candida albicans infection. J Infect Dis 220(9), 1477-1488.
Allert S*, Förster TM*, Svensson C-M, Richardson JP, Pawlik T, Hebecker B, Rudolphi S, Juraschitz M, Schaller M, Blagojevic M, Morschhäuser J, Figge MT, Jacobsen ID, Naglik JR, Kasper L, Mogavero S, Hube B; *authors contributed equally (2018) Candida albicans-induced epithelial damage mediates translocation through intestinal barriers. mBio 9(3), e00915.

Funding